It is the objective of this proposal to continue studies on the anticarcinogenic action of selenium in mammary neoplasia and to determine how the feeding of a high-fat diet can alter the chemopreventive efficacy of selenium. Our investigation involves the dimethylbenz(a)anthracene (DMBA)-induced mammary tumor model in female SD rats. Aim 1 is designed to compare different selenium compounds, both organic and inorganic, with respect to their effectiveness as chemopreventive agents. Furthermore, we are interested in finding out if the prophylactic potency of different selenium compounds is related to the levels of selenium in the mammary gland and blood. Aim 2 is designed to study the synergistic action of selenium and vitamin E in the inhibition of mammary tumorigenesis. This project is a follow-up of our previous observation that vitamin E is able to potentiate the anticarcinogenic action of selenium. First, we plan to find out if lower levels of vitamin E can be used without compromising its effectiveness, and secondly, to determine if the combination of selenium and vitamin E supplementation can obliterate the differential effect of high-fat and low-fat diets on mammary carcinogenesis. Finally, the effects of selenium/vitamin E supplementation on certain aspects of the host defense system as influenced by fat intake will be evaluated. Aim 3 is designed to delineate if the action of selenium is unique and distinct from other synthetic phenolic antioxidants such as butylated hydroxyanisole (BHA). The effects of selenium will be compared to some of the well known effects of BHA, specifically the selective induction of various liver enzymes that are responsible for the detoxification and inactivation of xenobiotics. Aim 4 is designed to determine if selenium stimulates the DNA repair mechanism after carcinogenic injury. We have previously demonstrated that suppression of mammary tumorigenesis was observed when selenium supplementation was limited to the time of carcinogen administration. We therefore plan to examine the effect of selenium on the binding of DMBA to mammary cell DNA and on the excision repair process as measured by unscheduled DNA synthesis. It cannot be overemphasized that a better understanding of the diverse action of selenium is essential before its usefulness in chemoprevention can be properly evaluated.